Our long-term objective is to improve human male reproductive health by designing, constructing, and marketing an automated digital imaging microscopy system for aneuploidy scoring of human sperm. Such a system would be used for testing the effects of toxic agents and for other research and clinical applications. Results from Phase I demonstrated technical feasibility to automatically detect chromosomes in sperm by integrating the latest technologies in image analysis software, computer hardware, automated microscopy and specialty multicolor fluorescence in situ hybridization (FISH) assays for sperm. The existing BioDx SlideScan(TM) system, which will serve as a basis for the proposed system, was evaluated and additional design requirements were identified. The specific aims in Phase II are to: 1) improve image analysis algorithms, 2) develop a rare event classification scheme, 3) perform system validation and 4) improve processing throughput. Factors that will drive the development of the proposed system include not only technical issues such as accuracy and processing throughput, but also ease-of-use and cost effectiveness.